It is the purpose of this project to conceive, conduct, and communicate the results of original research in the area of genetic manipulation of mammalian cells using the techniques of cell fusion, cellular hybridization and cybridization to produce unique material for the molecular genetic analysis of cellular events. Of prime importance in the laboratory now is the genetic system in mammalian mitochondria. The mapping of recombinations between mitochondrial DNA molecules is being studied using restriction enzymes and cRNA-DNA hybridization. The several distinctive subspecies of mouse are proving to be adequately marked material for such studies. Transformation to chloramphenicol resistance of chloramphenicol sensitive cell strains by mitochondrial DNA from chloramphenicol resistant mutant cell strains is being explored as a means of introducing new genes into mammalian cells so that the impact of such genetic surgery can be evaluated. We are also following the heritable consequences on cellular phenotypes of cytoplast fusion. Of special interest have been 1) the malignant phenotype and 2) the differentiated functions of normal thyroid cells. We are attempting to use direct microsurgical intervention (microinjection) in order to understand these phenomena.